MUNICH – Rivaroxaban (Xarelto) had no impact on outcomes of heart failure patients hospitalized for symptoms of worsening disease, according to a large, randomized trial with likely implications for other agents that prevent thrombin aggregation too.
In the more than 5,000 patients in the COMMANDER HF trial, there was no divergence of event rates between rivaroxaban and placebo as about 40% of patients from both arms of the trial experienced the primary composite endpoint of all-cause mortality, heart attack, or stroke (HR 0.94, 95%CI 0.84-1.05, P=0.27), reported Faiez Zannad, MD, PhD, of University Henri Poincaré in Nancy, France.
The two groups were similar for the components of the primary endpoint examined separately, although numerically there were marginally lower figures for all-cause mortality, myocardial infarction, and stroke with rivaroxaban, Zannad said at his press conference briefing at the annual meeting of the European Society of Cardiology. The findings were also released simultaneously in the New England Journal of Medicine.
When asked if a high dose of rivaroxaban might have produced better outcomes, Zannad said he didn't think it would "and we would have more adverse bleeding events." He suggested that outcomes with other agents in similar drug classes would have similar fates.
In commenting on the study, European Society of Cardiology spokesman Freek Verheugt, MD, told MedPage Today, "I agree that there is no role for the use of antithrombotics in these heart failure patients. These patients die from the underlying disease -- pump failure, arrhythmia. The thrombin problem in heart failure is a minor part of the disease process."
Verheugt said the COMMANDER HF trial is one of several that have attempted to modify the outcome of advanced heart failure patients using blood-thinning agents -- none of which have proved positive against the high rate of readmission to the hospital and high rates of death after an episode of worsening heart failure with reduced ejection fraction. He said studies have hinted that attacking thrombin formation in these patients might reduce those rates of death and rehospitalization.
"This is now definitely settled," Verheugt said. "COMMANDER was a large, beautifully-conducted study, but the drug doesn't work for these patients. I don't see that any other antithrombotic or anticoagulant would do any better."
The researchers randomly assigned 2,507 patients to receive rivaroxaban at a dose of 2.5 mg daily, while another 2,515 patients got placebo. The patients averaged about 66 years old; about 23% were women; 82% were white, and 14% were Asian. About 64% of the patients were recruited from nations in Eastern Europe; about 40% of the patients had reduced kidney function. About 93% of the patients were in New York Heart Association heart failure Class II or III. About 75% of the patients in the study had experienced a previous myocardial infarction; 40% were diabetic; 75% had been diagnosed with hypertension.
The patients were well-treated by guideline standards: 99% were taking diuretics; 93% were on angiotensin system inhibitors or blockers; 93% were on aspirin; 36% were on dual anti-platelet inhibition.
Zannad said that major bleeding episodes -- fatal bleeding or bleeding with potential to cause disability -- were not different statistically between the two arms of the study. More transfusions requiring two or more units of blood were needed by the rivaroxaban-treated patients compared with the placebo group (P=0.058). Hemoglobin reductions of 2 grams or more occurred significantly more often among the rivaroxaban patients, too.
The trial was supported by Janssen Research and Development.
Zannad disclosed relevant relationships with Janssen and Bayer.
Verheugt disclosed no relevant relationships with industry.